This program grant is based on our preliminary studies limiting high affinity antibodies reactive with the HIV-1 MN strains gp120 Primary Neutralizing Domain (gp120 MN PND) to reduced materno-fetal HIV transmission. This application includes two interrelated HIV transmission projects supported by two core facilities. The first project will assess high affinity antibodies to the gp120 MN PND in materno-fetal pairs infected by the HIV-1 MN strain. The phenotype and function of these antibodies will be evaluated in HIV infected pregnant women and their neonates. Fetal outcme (e.g. HIV infection status) will be correlated with levels of high affinity MN-PND antibodies, with their in vitro biological function (e.g. neutralization of HIV-1-MN) and with maternal virus load. Based on preliminary data previously obtained here showing a significant correlation between the lack of materno-fetal HIV transmission and the presence of these MN-PND antibodies, we propose in the second project to develop a materno-fetal HIV transmission blocking vaccine. For that purpose MN-PND peptides will be conjugated to tetanus toxoid or to PPD for immunization of HIV seropositive women who have a high robability of becoming pregnant within one year. The two supporting core facilities consist of (a) an vaccine production facility and an animal testing facility, and (b) a virus production, purification and neutralization core, in which HIV or its components will be obtained from patients and assays will be conducted to measure the biological function (e.g. HIV-1-MN neutralization, ADCC) of purified MN-PND antibodies and to assess the outcome of the MN-PND vaccine. If successful, this transmission blocking vaccine trial will later be expanded to sero-negative healthy individuals, alone or in conjunction with other vaccines such as the HIV-1 gag vaccine.